Comprehensive evaluation of the efficacy and safety of different vitamin D combination regimens based on indirect comparisons for children with rickets: a network meta-analysis
Abstract
Background: Nutritional rickets is a major pediatric bone disorder closely associated with vitamin D deficiency. Clinical practice has gradually shifted from vitamin D monotherapy toward combination regimens aiming to enhance therapeutic efficacy through complementary mechanisms. However, head-to-head evidence comparing different vitamin D-based combinations remains limited, and their relative efficacy and safety rankings are unclear.
Objective: To systematically compare the efficacy and safety of different oral vitamin D-based combination therapies for nutritional rickets in children and to provide evidence-based guidance for clinical decision-making.
Methods: We conducted a systematic search of PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases, followed by a Bayesian network meta-analysis. The study protocol was prospectively registered in PROSPERO (CRD420251029274).
Results: Ten randomized controlled trials involving 867 children were included, comparing nine vitamin D-based combination regimens with vitamin D3 monotherapy. Pairwise meta-analyses showed that combination therapies significantly improved serum 25-hydroxyvitamin D levels, reduced bone-specific alkaline phosphatase, and increased serum calcium and phosphate concentrations, without an increased risk of adverse events. Subgroup analyses indicated significantly greater benefits among term infants than preterm infants (P < 0.001). Network meta-analysis revealed distinct…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 867 participants or records.
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